Aims: Atrial fibrillation (AF) ablation is associated with increased circulating markers of
inflammation. Innate immune or inflammation pathways up-regulate mononuclear cell responses
and may increase the risk for recurrent arrhythmia. Chemokines and serine protease coagulation
pathways both activate innate immune responses. Here, we measured inflammatory markers in
peripheral blood samples from patients after cryoballoon and/or radiofrequency pulmonary vein
isolation and assessed the capacity for the inhibition of chemokine and serine protease pathways to
block cell activation.
Methods: Markers of inflammation were measured in 55 patients immediately before and one day
after AF ablation. Peripheral blood mononuclear cells (PBMCs) isolated from 19 patients were
further tested for responsiveness to two anti-inflammatory proteins ex vivo using fluorescence
assays and RT-qPCR analysis of gene expression.
Results: White blood cells (WBC), C-reactive protein, fibrinogen and troponin T levels were
significantly elevated after ablation. PBMCs isolated from the circulating blood had increased
activation with Phorbol 12-myristate 13-acetate. Cell activation, as measured by membrane fluidity,
was blunted after treatment with a broad-spectrum chemokine modulating protein, M-T7, which
interferes with chemokine/glycosaminoglycan (GAG) interactions, but not by Serp-1, a serine
protease inhibitor (serpin) that targets both thrombotic and thrombolytic pathway proteases.
Differential gene expression changes in the apoptotic pathway were identified with M-T7 and Serp-1.
Conclusions: Patients undergoing AF ablation have significantly increased inflammatory markers.
Inhibition of chemokine signaling, but not serine proteases, reduced the activation of monocytes
isolated from patients, in vitro. Targeting chemokines have the potential to reduce post-ablation
activation of circulating leukocytes.